Biology Reference
In-Depth Information
orangutan and gibbon only have a single copy consistent with a duplication of the
CMT1A-REP sequence after gorilla diverged from the human lineage but before
the divergence of chimpanzee and human (Kiyosawa and Chance, 1996).
Orthologous sequence comparison has provided evidence that the distal repeat
was the progenitor copy.
8.5.1 Duplications and the emergence of paralogous genes
During vertebrate evolution, novel genes have arisen by genome duplication
(tetraploidization; Chapter 2, section 2.1.1), intra-chromosomal regional duplica-
tion (Chapter 2, section 2.1.1), and localized individual gene duplication. All
three mechanisms give rise to
paralogous
genes, genes that occur within the same
species and which have a common ancestor. Paralogous genes therefore include
the members of multigene families and superfamilies. Evidence for the common
ancestry of paralogous genes may come from sequence homologies (e.g. as with
the voltage-sensitive ion channel genes; Strong
et al
., 1993) and/or from similar
exon-intron organization, for example the cholesterol ester transfer protein
(
CETP
; 16q21) and the phospholipid transfer protein (
PLTP
; 20q12-q13) (Tu
et
al
., 1995) genes, or the growth hormone receptor (
GHR
; 5p12-p14), prolactin
receptor (
PRLR
; 5p13-p14) and interferon receptor
,
, and
, 1 (
IFNAR1
;
21q22.1) genes (Lutfalla
et al
., 1992).
8.5.2 Intra-chromosomal regional duplication
In the human genome, whole chromosomal segments have sometimes been dupli-
cated (see Chapter 2, section 2.1) resulting in a series of paralogous genes retain-
ing their syntenic arrangement (Endo
et al
., 1997; Mazzarella and Schlessinger,
1997). Thus, a number of genes located at 6p21.3 have paralogous genes at 9q33-
q34 (Endo
et al
., 1997); the chromosome 6 loci include genes for type 11 collagen
2 subunit (
COL11A2
),
NOTCH4
, 70 kDa heat shock proteins (
HSPA1A
,
HSPA1B
,
HSPA1L
), valyl-tRNA synthetase 2 (
VARS2
), complement compo-
nents (
C2
,
C4A
,
C4B
), pre-B cell leukemia transcription factor 2 (
PBX2
) and
retinoid X receptor
(
RXRB
) whilst the chromosome 9 paralogues include
COL5A1
,
NOTCH1
,
HSPA5
,
VARS1
,
C5
,
PBX3,
and
RXRA
. Other extensive
chromosomal duplications included genomic segments present at Xq28 and
16p11.1 involving the paralogous creatine transporter genes
SLC6A8
and
SLC6A10
respectively (Eichler
et al
., 1996).
Some intra-chromosomal duplications may only involve one or a small number of
genes, for example the duplication of the iduronate-2-sulphatase (
IDS
) locus at Xq28
(Timms
et al
., 1995; Bondeson
et al
., 1995). Another example is that of the inverted
duplication at 5q13 which duplicated the spinal muscular atrophy (
SMA
) gene, the
survival motor neuron (
SMN
) gene and the apoptosis inhibitory protein (
NAIP
) gene
(Campbell
et al
., 1997). Duplicated paralogous genes may however be translocated to
quite different locations on the same chromosome, for example the adrenergic recep-
tor (
ADRA1B
and
ADRB2
) genes on 5q23-q32 are quite distant from the evolution-
arily related serotonin receptor (
HTR1A
) gene on 5cen-q11 (Oakey
et al
., 1991).
